Exogenous Sulfite Research Articles

Design and application of a novel “turn-on” fluorescent probe for imaging sulfite in living cells and inflammation models

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

A ratiometric fluorescent sensor based on carbon dots for rapid determination of bisulfite in sugar

Sulfite is widely used in food and drugs as a preservative; however, excessive intake of exogenous sulfite is harmful to human health. Hence, developing effective methods to detect sulfite and its derivatives is vital. Herein, we present a ratiometric fluorescent sensor for bisulfite based on a dual-emission boron-nitrogen double-doped carbon dots (BNCDs)-Cr(VI) system. After adding bisulfite, the fluorescence intensity at 450 nm was significantly enhanced because of the inhibition of the inner filter effect, while the fluorescence emission at 535 nm decreased. A sensor-based method was developed to determine bisulfite with a linearity range of 0 – 10.0 × 102 μmol/L and recoveries of 97.33% – 109.00%, achieving the quantitative detection of bisulfite in real sugar samples. Moreover, a paper test strip-based visual measuring system for bisulfite was developed, which realized the rapid and semiquantitative detection of bisulfite.

Imaging fluctuation of sulfite in mouse tumor and inflammation models with a novel quinoxaline-based fluorescent probe

In this work, a novel fluorescent probe, YT, was developed for monitoring the fluctuation of sulfite in biological applications. The quinoxaline moiety was chosen as the fluorophore to obtain the naked-eye signals in the green channel. The levulinate was selected to achieve the specific and relatively steady recognition reaction. Compared with the reported fluorescent probes for sulfite, YT indicated above moderate performances including remarkable and rapid response (120 folds, within 10 min), high sensitivity (limit of detection = 0.15 μM), and high selectivity. The detecting system showed a green emission and the fluorescence was stable within the pH range of 6–10. In addition, YT could be further applied into living cells and mouse models. Focusing on the serviceability in the breadth of application scope, we imaged the fluctuation of sulfite in both mouse tumor and inflammation models. In the xenograft model, YT could indicate the fluctuation of sulfite which was caused by both addition of exogenous sulfite and induction of different agents including sulfite donor, Na2S2O3, phorbol-12-myristate-13-acetate, and GSH. In the LPS-induced inflammation model, YT could visualize the dose-dependent increase of sulfite level (0–2 mg/mL). More than providing a practical fluorescent implement for monitoring sulfite, this work also raised informatic parameters for developing fluorescent tools into broadened animal models.

Extracellular sulfite is protective against reactive oxygen species and antibiotic stress in Shewanella oneidensis MR-1.

In this study, we investigated the extracellular reactive sulfur species produced by Shewanella oneidensis MR-1 during growth. The results showed that sulfite is the major extracellular sulfur metabolite released to the growth medium under both aerobic and anaerobic growth conditions. Exogenous sulfite at physiological concentrations protected S. oneidensis MR-1 from hydrogen peroxide toxicity and enhanced tolerance to the beta-lactam antibiotics cefazolin, meropenem, doripenem and ertapenem. These findings suggest that the release of extracellular sulfite is a bacterial defence mechanism that plays a role in the mitigation of environmental stress.

Biological applications of a turn-on bioluminescent probe for monitoring sulfite oxidase deficiency in vivo

Sulfites are widely used as preservative and antioxidant additives in food and drug. A non-invasive method for in vivo imaging of sulfite represents a powerful tool for estimating its potential effects in living organisms. Herein, we report the design, development, and application of sulfite bioluminescent probes (SBPs) for the analyte-specific detection of sulfite through sulfite-mediated intramolecular cleavage. Among them, SBP-1 exhibited the excellent responsivity, high selectivity and sensitivity. By taking advantage of this probe, the first in vivo imaging of sulfate was successfully carried out, not only to trace exogenous sulfite level in living animal, but also to investigate endogenous sulfite in a sulfite oxidase deficiency model.

Anaphylaxis due to sulfite intolerance: a protective effect from cyanocobalamin

Background The mechanisms of sulfite intolerance are unknown. It has been suggested that, in some cases, it could be due to a partial sulfite-oxidase deficiency. In these patients, this enzyme is unable to metabolize adequately an overload of ingested or inhaled exogenous sulfite, triggering a bronchospasm. Cyanocobalamin is able to catalyze the extracellular oxidation of sulfites, preventing sulfite accumulation and the subsequent symptoms due to this excess.

An Essential Role for Tomato Sulfite Oxidase and Enzymes of the Sulfite Network in Maintaining Leaf Sulfite Homeostasis

Little is known about the homeostasis of sulfite levels, a cytotoxic by-product of plant sulfur turnover. By employing extended dark to induce catabolic pathways, we followed key elements of the sulfite network enzymes that include adenosine-5'-phosphosulfate reductase and the sulfite scavengers sulfite oxidase (SO), sulfite reductase, UDP-sulfoquinovose synthase, and β-mercaptopyruvate sulfurtransferases. During extended dark, SO was enhanced in tomato (Solanum lycopersicum) wild-type leaves, while the other sulfite network components were down-regulated. SO RNA interference plants lacking SO activity accumulated sulfite, resulting in leaf damage and mortality. Exogenous sulfite application induced up-regulation of the sulfite scavenger activities in dark-stressed or unstressed wild-type plants, while expression of the sulfite producer, adenosine-5'-phosphosulfate reductase, was down-regulated. Unstressed or dark-stressed wild-type plants were resistant to sulfite applications, but SO RNA interference plants showed sensitivity and overaccumulation of sulfite. Hence, under extended dark stress, SO activity is necessary to cope with rising endogenous sulfite levels. However, under nonstressed conditions, the sulfite network can control sulfite levels in the absence of SO activity. The novel evidence provided by the synchronous dark-induced turnover of sulfur-containing compounds, augmented by exogenous sulfite applications, underlines the role of SO and other sulfite network components in maintaining sulfite homeostasis, where sulfite appears to act as an orchestrating signal molecule.

Sulfite Oxidation in Chlorobaculum Tepidum

The green sulfur bacterium Chlorobaculum tepidum is proposed to oxidize sulfide and elemental sulfur via sulfite as an obligate intermediate. The sulfite pool is predicted to be contained in the cytoplasm and be oxidized by the concerted action of ApsBA, which directly oxidizes sulfite, and QmoABC, which transfers electrons from ApsBA to the quinone pool. Like other green sulfur bacteria, C. tepidum was unable to use exogenously provided sulfite as the sole electron donor. However, exogenous sulfite significantly stimulated the growth yield of sulfide limited batch cultures. The growth of C. tepidum mutant strains, CT0867/qmoB::TnOGm and CT0868/qmoC::TnOGm, was not increased by sulfite. Furthermore, these strains accumulated sulfite and displayed a growth yield decrease when grown on sulfide as the sole electron donor. These results support an obligate, cytoplasmic sulfite intermediate as part of the canonical sulfur oxidation pathway in C. tepidum that requires the Qmo complex for oxidation.

Effect of sulfite on antioxidant enzymes and lipid peroxidation in normal and sulfite oxidase-deficient rat erythrocytes

Sulfite and related chemical such as sulfite salts and sulfur dioxide has been used as a preservative in food and drugs. This molecule has also been generated from the catabolism of sulfur-containing amino acids. Sulfite is a very reactive and potentially toxic molecule and has to be detoxified by the enzyme sulfite oxidase (SOX). The aim of this study was to investigate the effects of ingested sulfite on erythrocyte antioxidant status by measuring glucose-6-phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant status by measuring thiobarbituric acid reactive substances (TBARS) in normal and SOX-deficient rats. Rats were assigned to four groups (n = 10 rats/group) as follows; control (C), sulfite (CS), deficient (D), and deficient + sulfite (DS). SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25 mg/kg) was administered to the animals via their drinking water. At the end of 6 weeks, Erythrocyte G-6-PD, SOD, and GPx but not CAT activities were found to be significantly increased with and without sulfite treatment in SOX-deficient groups. Sulfite treatment alone was also significantly increased erythrocytes' SOD activity in CS group compared to control. TBARS levels were found to be significantly increased in CS and DS groups and decreased in D group. When SOX-deficient rats treated with sulfite, TBARS level was still higher than other groups. In conclusion, these results suggested that erythrocyte antioxidant capacity, a defense mechanism against the oxidative challenge, increased by endogenous and exogenous sulfite due to its oxidant nature. This increase was also observed in CS and DS groups but it was insufficient to prevent lipid peroxidation.

Expressions of N-methyl-d-aspartate receptors NR2A and NR2B subunit proteins in normal and sulfite-oxidase deficient rat’s hippocampus: effect of exogenous sulfite ingestion

Sulfites whether ingested or produced through the sulfur-containing amino acids metabolism of the animal are very active molecules and can cause cellular toxicity. Sulfite oxidase (SOX), a heme- and molybdenum containing mitochondrial enzyme, prevents mammalian cells from adverse effects of sulfite toxicity by metabolizing sulfite to sulfate. The present study was aimed to investigate effect of sulfite on the N-methyl-D-aspartate (NMDA) receptor (NMDAR) NR2A and NR2B subunits in hippocampus of normal and SOX-deficient rats. Rats were divided into four groups; (1) control group, which was given rat chow and tap water ad libitum (C), (2) sulfite group, treated with sulfite (25 mg/kg) in drinking water and commercial rat chow ad libitum (S), (3) SOX-deficient group, maintained on high-W/Mo-deficient regimen to produce SOX deficiency (D), and (4) SOX-deficient + sulfite group (DS), prepared as those in the third group and were afterwards given sulfite (25 mg/kg) additionally. Whole treatment schedule were continued for 6 weeks. Sulfite treatment caused a decrease of NR2A and NR2B subunits of the NMDAR in hippocampus of rats in S and DS groups. Interestingly, similar decrement was observed in D group, probably due to increased endogenous sulfite production. In summary, the results indicated that feeding sulfite to the rats may cause down-regulation of NMDARs by degrading NR2A and NR2B subunits of it, which may be considered as a neuro-compensatory mechanism.

Elevated levels of serum sulfite in patients with chronic renal failure.

Sulfite, a well known air pollutant, is toxic for humans, especially those with sulfite hypersensitivity. Sulfite is also generated endogenously, during normal metabolism of sulfur-containing amino acids. Mammalian tissues contain the enzyme sulfite oxidase, which detoxifies both endogenous and exogenous sulfite by oxidation to sulfate. Deficiency of sulfite oxidase in humans is fatal, demonstrating its physiologic importance. Nevertheless, information about serum and tissue levels of sulfite in normal and pathologic conditions is limited. Using a sensitive HPLC assay, it is shown here that sera from patients with chronic renal failure (CRF) contain significantly higher amounts of sulfite than those from healthy subjects. Mean +/- SD of serum sulfite in healthy subjects (n = 20) was 1.55 +/- 0.54 microM, whereas those in patients under maintenance hemodialysis (HD patients; n = 44) and CRF patients before introducing dialysis therapy (pre-HD patients; n = 33) were 3. 23 +/- 1.02 microM (P < 0.01) and 3.80 +/- 3.32 microM (P < 0.01), respectively. Among pre-HD patients, serum sulfite was positively correlated with serum creatinine (r = 0.714, P < 0.0001), and negatively with serum albumin (r = -0.407, P = 0.0188), hematocrit (r = -0.524, P = 0.0017), and total cholesterol (r = -0.375, P = 0. 0318). There was no significant association between sulfite and patient age, gender, or leukocyte counts. Multiple regression analysis revealed serum creatinine as the sole independent predictor of serum sulfite levels. Each HD treatment was associated with approximately 27% reduction in serum sulfite levels, suggesting the presence of a dialyzable form in serum. Thus, these results indicate that reduced glomerular filtration is a factor that determines serum sulfite levels. Chronic elevation in serum sulfite levels might contribute to tissue or organ dysfunction in patients with CRF.

Enhanced amyloidogenicity of sulfonated transthyretin in vitro, a hypothetical etiology of senile amyloidosis

Genetic variants of transthyretin (TTR) cause systemic amyloidosis and wild-type TTR may also in some situations produce amyloid fibrils. We have analyzed wild-type and variant TTRs by mass spectrometry and found that TTR preparations from all individuals demonstrated free TTR, TTR conjugated with thiol compounds and several minor components. We previously described a component which had a molecular mass 80 Da larger than free TTR and was proved to be TTR conjugated with sulfite. Here, the amyloid fibril formation of the TTR isoforms was monitored by the turbidity at 330 nm, and by a Congo red-binding assay as a function of pH, according to the method of Lai et al. The S-sulfonated TTR showed the highest level of amyloid fibril formation. In contrast, TTR reduced by dithiothreitol, which was free of the S-sulfonated component, showed neither elevation of the turbidity nor the Congo red binding. Commercially purchased TTR without further treatment containing free, S-sulfonated and other species of TTR molecules showed an intermediate elevation. These results suggested that the S-sulfonated wild-type TTR is highly amyloidogenic. Although further experiments are needed to apply the observation to in vivo phenomenon, exogenous sulfite may be a cause of senile systemic amyloidosis.

Sulfite hypersensitivity. A critical review.

Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity.